Project 3: Expression of developmentally regulated proteins in hypoxia. Chronic hypoxia in the early postnatal period is becoming an increasingly frequent occurrence. The neurodevelopmental consequences of early hypoxia can be severe. If we are to develop strategies to prevent the cognitive and behavioral deficits that result from early postnatal hypoxia, we must first gain a better understanding of the neurobiological consequences of hypoxic insult. In this project we will consider the effects of early hypoxia on the development of the molecular composition of the brain. We will compare normal to hypoxic animals through development and into adulthood to determine if hypoxia induces alterations in the normal time course of expression of several neural proteins and genes. Preliminary studies have shown that the expression of several important developmentally regulated proteins in perturbed by neonatal hypoxia. Abnormal structure/function of the brain as a consequence of insult in the early postnatal period could reflect a delay in normal developmental processes, or a precocious arrest of development. Either of these mechanisms would lead to the abnormalities observed in the hypoxic model used here. The first aim of this project is to determine if periods of early postnatal hypoxia lead to abnormalities in the expression of developmentally regulated neural proteins. The results of these experiments will permit us to distinguish between developmental delay and developmental arrest as potential mechanisms underlying alterations caused by early postnatal hypoxia. "Critical periods" in development, during which the structure and function of neurons can be modified by neuronal activity, have been documented in many areas of the nervous system. Abnormal neuronal activity during these critical periods can lead to irreversible abnormalities in neuronal structure and function. In considering management of infants with early postnatal hypoxia, it is essential to determine if there is a "critical period" during which hypoxia lead to permanent neurological abnormalities. The second aim of this project is to determine if there are "critical periods" for the abnormalities that result from hypoxia. We will establish the time window during which hypoxia produces irreversible changes in neural properties.